Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine

Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive–compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder

Quantum phase transitions of light

Recently, condensed matter and atomic experiments have reached a length-scale and temperature regime where new quantum collective phenomena emerge. Finding such physics in systems of photons, however, is problematic, as photons typically do not interact with each other and can be created or destroyed at will. Here, we introduce a physical system of photons that exhibits strongly correlated dynamics on a meso-scale. By adding photons to a two-dimensional array of coupled optical cavities each containing a single two-level atom in the photon-blockade regime, we form dressed states, or polaritons, that are both long-lived and strongly interacting. Our zero temperature results predict that this photonic system will undergo a characteristic Mott insulator (excitations localised on each site) to superfluid (excitations delocalised across the lattice) quantum phase transition. Each cavity's impressive photon out-coupling potential may lead to actual devices based on these quantum many-body effects, as well as observable, tunable quantum simulators. We explicitly show that such phenomena may be observable in micro-machined diamond containing nitrogen-vacancy colour centres and superconducting microwave strip-line resonators.Comment: 11 pages, 5 figures (2 in colour

Impact of temporary desiccation on the mobility of nutrients and metals from sediments of Loskop Reservoir, Olifants River

South Africa is prone to droughts and is heavily dependent on stored water resources. Few studies in South Africa have investigated the impact of drought on water quality when rainfall resumes and reservoir sediments are rewet. Other research has shown that several negative impacts may occur with rewetting, including eutrophication, and acidification with increased metal solubility. In this study, the impact of drying and rewetting sediments on the mobility of nutrients and metals is explored using sediments from Loskop Reservoir. Rarely exposed sediments were collected from three sites, dried at 35°C for 36 days, and then rewet under aerobic conditions. Filtered water samples were collected on Days 1, 2 ,4, 7, 11 and 16 following rewetting, and analysed for NH4+, NO3-, NO2-, total N, total P, PO43-, dissolved Al, Fe, Mn, and SO42-. Results were expressed as mass/m2, and were compared to reference (non-drought) treatments that were maintained under saturated conditions. Acute toxicity tests were performed using Daphnia magna to establish if toxic effects were associated with changes in water quality following sediment rewetting. Following rewetting, elevated SO42- indicated the mobilisation of acid from sulfide oxidation, with an associated reduction in pH. Nitrification was evident as high quantities of organic N and NH4+ were initially released, followed by increases in NO2- + NO3-. Total P increased, but PO43- reduced. This was attributed to complexes formed between PO43- and Fe (FePO4) and Al (AlPO4). Amounts of Fe and Al released were lower following rewetting due to the formation of relatively immobile (hydr)oxides. In contrast, Mn increased substantially reaching maximum values > 2 300 mg/m2 (14 000 μg/L). There were no acute toxic effects observed to D. magna. This study highlights the potential for acidification, mobilisation of nutrients, SO42-, and Mn following rewetting of reservoir sediments under aerobic conditions. This information may be incorporated into reservoir and catchment management plans in the form of revised water quality guidelines and a better ability to predict how drought impacts water quality in our stored water resources.Keywords: sediment, drought, drying, rewetting, nutrient and metal release, Loskop Reservoi

Cold gas accretion in galaxies

Evidence for the accretion of cold gas in galaxies has been rapidly accumulating in the past years. HI observations of galaxies and their environment have brought to light new facts and phenomena which are evidence of ongoing or recent accretion: 1) A large number of galaxies are accompanied by gas-rich dwarfs or are surrounded by HI cloud complexes, tails and filaments. It may be regarded as direct evidence of cold gas accretion in the local universe. It is probably the same kind of phenomenon of material infall as the stellar streams observed in the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI have been found in nearby spiral galaxies. While a large fraction of this gas is produced by galactic fountains, it is likely that a part of it is of extragalactic origin. 3) Spirals are known to have extended and warped outer layers of HI. It is not clear how these have formed, and how and for how long the warps can be sustained. Gas infall has been proposed as the origin. 4) The majority of galactic disks are lopsided in their morphology as well as in their kinematics. Also here recent accretion has been advocated as a possible cause. In our view, accretion takes place both through the arrival and merging of gas-rich satellites and through gas infall from the intergalactic medium (IGM). The infall may have observable effects on the disk such as bursts of star formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates needed to sustain the observed star formation (~1 Msol/yr), additional infall of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages. Full-resolution version available at http://www.astron.nl/~oosterlo/accretionRevie

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Greater number of group identifications is associated with lower odds of being depressed: evidence from a Scottish community sample

Purpose: Group identification has been shown to be associated with reduced risk of depression, but this research has important limitations. Our aim was to establish a robust link between group identification and depression whilst overcoming previous studies’ shortcomings. Methods: 1824 participants, recruited from General Practice throughout Scotland, completed a questionnaire measuring their identification with three groups (family, community, and a group of their choice), as well as their intensity of contact with each group. They also completed a self-rated depression measure and provided demographic information. Their medical records were also accessed in order to determine if they had been prescribed antidepressants in the previous six months. Results: Number of group identifications was associated with both lower self-rated depression and lower odds of having received a prescription for antidepressants, even after controlling for number of contact-intensive groups, level of education, gender, age, and relationship status. Conclusions: Identifying with multiple groups may help to protect individuals against depression. This highlights the potential importance of social prescriptions, where health professionals encourage a depressed patient to become a member of one or more groups with which the patient believes he/she would be likely to identify

Multiple ITS Copies Reveal Extensive Hybridization within Rheum (Polygonaceae), a Genus That Has Undergone Rapid Radiation

During adaptive radiation events, characters can arise multiple times due to parallel evolution, but transfer of traits through hybridization provides an alternative explanation for the same character appearing in apparently non-sister lineages. The signature of hybridization can be detected in incongruence between phylogenies derived from different markers, or from the presence of two divergent versions of a nuclear marker such as ITS within one individual.In this study, we cloned and sequenced ITS regions for 30 species of the genus Rheum, and compared them with a cpDNA phylogeny. Seven species contained two divergent copies of ITS that resolved in different clades from one another in each case, indicating hybridization events too recent for concerted evolution to have homogenised the ITS sequences. Hybridization was also indicated in at least two further species via incongruence in their position between ITS and cpDNA phylogenies. None of the ITS sequences present in these nine species matched those detected in any other species, which provides tentative evidence against recent introgression as an explanation. Rheum globulosum, previously indicated by cpDNA to represent an independent origin of decumbent habit, is indicated by ITS to be part of clade of decumbent species, which acquired cpDNA of another clade via hybridization. However decumbent and glasshouse morphology are confirmed to have arisen three and two times, respectively.These findings suggested that hybridization among QTP species of Rheum has been extensive, and that a role of hybridization in diversification of Rheum requires investigation

Which outcomes should be included in a core outcome set for capturing and measuring doctor well-being? A Delphi study

This is the final version. Available from BMJ Publishing via the DOI in this record. Data availability statement: All data relevant to the study are included in the article or uploaded as supplementary information.Objectives: To develop a core outcome set (COS) to capture and measure the well- being of doctors working in the National Health Service (NHS). Design: An online Delphi study. Setting: UK NHS. Participants: Participants from four stakeholder groups: (1) those who might use the COS in research, (2) organisations that measure/capture NHS staff well- being, (3) professionals with experience managing NHS staff well- being and (4) NHS doctors were identified through authorship of relevant publications, attendee lists of doctor well- being conferences and meetings, professional bodies, participation in a previous study and recommendations from others. They were recruited via email. Interventions: A two- stage process: (1) creating a list of 43 well- being outcomes informed by a systematic review of well- being measurement instruments, a survey of UK doctors and two doctor engagement workshops and (2) an online Delphi study (with two rounds) to reach consensus. Outcomes were rated on a 9- point Likert scale; ‘consensus’ was reached when ≥75% agreed that an outcome was critical for inclusion in the COS. Results: 52 participants completed both Delphi rounds. Seven well- being outcomes met the threshold for inclusion in the COS: general well- being, health, personal safety, job satisfaction, morale, life work balance and good clinical practice. Conclusions: Use of the COS has the potential to reduce heterogeneity and standardise the capture and measurement of doctor well- being, and ensure outcomes important to all stakeholders are reported.Health Education EnglandNational Institute for Health Research (NIHR

Health-seeking behaviours of older black women living with non-communicable diseases in an urban township in South Africa

BACKGROUND: Various studies have shown that non-communicable diseases (NCDs) especially diabetes and hypertension are prevalent among older women living in South African urban areas, placing a heavy burden on the healthcare system. This study aimed to understand the health-seeking behaviour, healthcare practices and prevalence of traditional herbal medicine (THM) use among older women self-reporting NCDs from the Prospective Urban Rural Epidemiology study (PURE). METHOD: A homogenous purposive sampling of PURE participants was used to recruit women who were 50 years or older (n = 250). Descriptive statistics were used to examine the number of NCDs reported by the study sample, health seeking behaviour and practices as well as THM use. Logistic regression was also employed to investigate possible associations between reported conditions and THM use or medical pluralism. RESULTS: Within the study sample, 72 % self-reported an NCD. Of those with self-reported NCDs, 46 % had one, and 54 % had two or more NCDs. Those with NCDs usually visited public clinics (80 %), relied on doctors (90 %) and nurses (85 %) for health information, and mostly used conventional medicine (CM) to manage high blood pressure (81 %). About 30 % of those with NCDs indicated using THM, of whom 29 (53 %) reported practicing medical pluralism. Participants with dental problems (OR: 3.24, 95 % CI: 1.30–8.20), headaches (OR: 2.42, 95 % CI: 1.24–4.94), heart burn (OR: 2.30, 95 % CI: 1.18–4.48) and severe tiredness (OR: 2.05, 95 % CI: 1.08–3.99) were more likely to use THM. Anxiety and allergies increased the likelihood to practise medical pluralism by five and 20 times, respectively. CONCLUSION: Self-reported NCD with co-morbidities was prevalent among the participants in the study. Most of the study participants utilized state-owned clinics and hospitals for the management of their chronic conditions. THM use was not very common. However, among those who used THM, medical pluralism was prevalent. Family history was the most common reason for THM use, with many THM patrons utilizing these for treatment of a health condition. Older black women with anxiety and allergies were more likely to practise medical pluralism